A Phase 4 Multi-center, Ascending Dose, Open Label Study to Determine the Pharmacokinetics of Phenylephrine and the Pharmacodynamic Effects on Blood Pressure following Intravenous Administration of Phenylephrine Hydrochloride Injection, USP in Pediatric Subjects (≥12 to 16 years of age) Undergoing General and Neuroaxial Anesthesia

Study subjects will be scheduled for procedures requiring general or neuroaxial anesthesia. Subjects will be non-shock, non-trauma patients, with no history of Tetralogy of Fallot. in order to be treated, subjects must experience a decrease in BP during the procedure that requires drug intervention. PHi will be administered to six successive cohorts with 16 to 17 subjects in each cohort. The first three successive cohorts (1, 2, and 3) will receive infusion treatments. after the infusion is initiated, a minimum infusion time of 10 minutes (approximately 2 to 3 times the distribution half-life, approaching steady state) will permit meaningful assessments of safety and pharmacodynamic responses. The second three successive cohorts (4, 5, and 6) will receive bolus treatments. according to the approved labeling for adults, the onset of BP increase following administration of a bolus dose is rapid. in this study, a minimum time interval of 2 minutes will be allowed in order to assess response before further doses are administered. Safety assessments include adverse events (aes) and laboratory test results. Safety will be evaluated by the Cohort Review Committee (CRC) after each dosing level cohort completes the study, and approval will be granted for the next cohort to begin treatment at a higher dose. Following completion of Cohort 3, the highest dosing level for infusion treatment, the Data Safety Monitoring Board (DSMB) will review both safety data and PK data before approving treatment with bolus doses. The proposed bolus doses will be reviewed in order to assure that the projected Cmax values will be lower than the Cmax for the completed infusion cohorts.